ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.318G>A (p.Trp106Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004701787 SCV005205680 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-10 reviewed by expert panel curation NM_001754.5(RUNX1):c.318G>A (p.Trp106Ter) is a nonsense variant which is predicted to undergo nonsense-mediated decay (as per the modified RUNX1 PVS1 decision tree) (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). It is a nonsense variant that is downstream of c.98 (PM5_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_Supporting; PMID: 34233450). In summary, this variant meets the criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_Supporting, PM5_Supporting, PS4_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV003630952 SCV004455701 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-10-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp106*) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. For these reasons, this variant has been classified as Pathogenic.

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